K.E.M. Radiology

Interventional Case Record

< Case 18 : December 2020 >

Contributed by Punit Mahajan

Other cases

Adrenal Venous sampling in a clinically suspected case of primary hyperaldosteronism

Introduction:

There is an increasing requirement for adrenal vein sampling, which is driven by the appreciation that primary aldosteronism is far more common than previously recognized (1-3). Many centres throughout the world are reporting a prevalence of between 5% and 10% in unselected hypertensive patients (4-8). Historically, adrenal vein sampling has been problematic, with many authors reporting difficulties with obtaining good samples, particularly from the right adrenal vein (9-11). This results from the small size of the right adrenal vein and the resulting difficulty in obtaining an adequate specimen, recognizing the typical vascular patterns, and distinguishing other vessels that may arise from the posterior wall of the inferior vena cava (IVC) close by. Lastly, the long anatomic segment that may give rise to the right adrenal vein may result in a prolonged search pattern. Superimposed on this is the frequency of anatomic variations of the left renal vein or left adrenal vein (12). Cure of hypertension occurs in 50%– 80% of patients after adrenalectomy for an aldosterone producing adenoma, and most of the remaining cases show improvement. Cases of bilateral aldosterone hypersecretion can usually be controlled simply with specific medications (1–3)

Case presentation:

A 50-year-old woman was referred to our endocrinologists for investigation of resistant hypertension, which had been present since she was 33 years of age,. The patient also had persistent hypokalaemia. She was on multiple anti-hypertensive medications both alpha 2 agonists and beta blockers. She also had a long-term history of on and off headaches. Her physical examination was normal, except for high blood pressure. Her serum creatinine and renal function tests were within normal limits. 2D Echocardiography and renal artery Doppler were also within normal limits. Biochemical investigations showed high aldosterone to renin ratio leading to the suspicion of of primary hyperaldosteronism. An abdominal CT scan showed a subcentimeter enhancing nodule measuring 8 x 6 mm in the right adrenal gland. (Fig. 1) The left adrenal gland was normal.

The patient underwent adrenal venous sampling using cosyntropin stimulation. Blood samples were obtained sequentially under fluoroscopic guidance. There was difficulty in obtaining the sample from the right adrenal vein due to its small calibre, which led to sampling from the vein’s ostium. Peripheral samples for aldosterone and cortisol were also obtained from the inferior vena cava. Blood samples were labelled and sent for analysis of cortisol and aldosterone function.

On the right side initially, catheter was placed just at the orifice of the main adrenal venous trunk and was therefore able to stain adrenal vein tributaries. Samples were obtained initially by placing the catheter tip at the outflow of the main adrenal vein trunk and then by deeply inserting the catheter in both of the secondary tributaries and selectively cannulating them using a microcatheter (Fig. 2). Samples from the right-side selective branch showed a high cortisol-corrected aldosterone concentration. The left-sided sample was obtained under Valsalva manoeuvre to see the tributaries of left renal vein and then the left adrenal vein is selectively cannulated using microcatheter (Fig. 3). It showed low cortisol corrected aldosterone concentration that was less than that measured in the IVC. In view of these findings, the patient underwent right sided adrenalectomy with no intra or post-operative complications. Post-operative follow-up showed decreased requirement of the anti-hypertensive medication to a single drug.

Discussion:

Indications:

The endocrine society recommends adrenal venous sampling to confirm unilateral disease in all patients with primary aldosteronism who would like to pursue surgical management in form of unilateral adrenalectomy.

As per the literature in few of the centres approach is slightly different, they recommend AVS in such patients when the CT scan is normal, shows bilateral abnormalities, or shows unilateral abnormality, but patients age is over 40 years. (17)

Contraindications:

1. Patient prefers lifelong medical treatment.

2. Young patients (e.g. patient less than 40 years with recent onset primary aldosteronism and clear-cut unilateral cortical adenoma on imaging)

3. Proven familial hyperaldosteronism type I or III.

4. Poor surgical candidate for adrenalectomy.

5. Adrenocortical Carcinoma.

6. Patient accepts a 20-50% chance of having the wrong adrenal removed.

Anatomy of the veins:

Right adrenal vein: Normally there is a central vein which drains directly at the mid-posterior wall of inferior vena cava. The central vein may be duplicated with some veins draining to inferior phrenic or right renal vein. However, there is almost always a central vein entering the IVC. It is 1 -15 mm in length and averages 3.5 – 5 mm in diameter.

These are some of the patterns helpful to recognize the right adrenal vein

Gland-like pattern with main central stem and numerous branches,

Delta pattern with a little filling of the internal structure, Triangular pattern, central vein with thin stellate or spidery branches.

Presence of superficial or emissary veins from the adrenal capsule. It provides high confidence of confirmation. The emissary vein may communicate with the right renal vein, intercostal vein, phrenic vein, or IVC. The inferior emissary vein serves as a reliable landmark for right adrenal vein. The veins should not communicate with the hepatic vein. (12,13)

Left adrenalvein – It drains into the left renal vein and most of the times have a common trunk with the inferior phrenic vein. It is 1 – 4 cm in length and averages 4-5 mm in diameter. CT can be helpful to look for any variation of left renal vein like retro aortic/circumaortic renal vein. (12,13)

Adrenal vein sampling (AVS) is the gold standard assay to distinguish unilateral from bilateral adrenal sources of autonomous aldosterone secretion. According to consensus guidelines, AVS should be performed in all patients with an established diagnosis of PA in whom adrenalectomy is being considered, except for young (less than 40 years old) patients with severe PA and clear findings on cross-sectional imaging or for patients with findings suspicious for adrenocortical carcinoma.

Sampling is performed from each adrenal vein (AV) and the inferior vena cava (IVC) sequentially, or simultaneously. Simultaneous sampling has the theoretical advantage of eliminating temporal fluctuations in hormone secretion, and necessitates bilateral common femoral venous access. Simultaneous sampling can increase the technical challenge of AVS, as maintaining access in both AVs may prove difficult. These challenges may be minimized with sequential sampling, which is typically performed during infusion of cosyntropin, a synthetic analogue of ACTH that stimulates the adrenal gland to secrete cortisol and aldosterone and increases the sensitivity and specificity of AVS. Thus, most centres use sequential sampling with cosyntropin stimulation. In this technique, a 5 or 6 French vascular sheath is placed in the right common femoral vein, allowing for passage of 4 and 5 French catheters to direct into each AV. A peripheral specimen may be obtained from the IVC or the groin sheath once the AV specimens are collected. Cosyntropin infusion should be initiated at least 30 minutes prior to any sampling.

Because the right AV originates directly from the IVC, whereas the left AV originates from the left renal vein, the right AV is technically more challenging to cannulate and is typically assessed first. A variety of catheters may be needed to find the right AV, whereas usually a Simmons-2 catheter will readily cannulate the left AV. After being advanced into the renal vein, the Simmons catheter can be slowly withdrawn until it falls into the common venous trunk emptying both the inferior phrenic and left AV. Sampling may be performed in the common trunk, or a microcatheter may be used to select the AV. Strategies for finding the right AV are detailed later in the section describing AVS pearls. Catheter position is confirmed with gentle hand injections, and power injections are never performed. Usually, multiple specimens are taken from candidate right AVs, and one or two samples from the left AV and/or common trunk. Specimens should not be transported on ice, but should be maintained in specific tubes requested by the laboratory, agreed upon with laboratory staff prior to the procedure.(13-16)

An initial pigtail catheter inferior vena cava gram in the expected position of the right adrenal vein (AV) can sometimes demonstrate the position of the AV origin, as a small focus of contrast pooling. Various catheters may be necessary to cannulate it, including reverse curve catheters and microcatheters. Proper recognition of right adrenal venography patterns is critical: injection may reveal a central stem with branches in a gland-like pattern, a triangular pattern with parenchymal blush, a delta pattern without parenchymal blush, or a central vein with stellate branches. (14) Typically, inferolaterally or medially oriented emissary veins will emerge from the right adrenal vein from the adrenal capsule and communicate with the renal or phrenic veins, IVC, or intercostal veins. If upward-sloping branches are seen, this suggests cannulation of the accessory hepatic vein. Selecting the inferior accessory hepatic vein is a common occurrence during the search for the right adrenal vein (AV); fortunately, this may be used as a helpful anatomic landmark, as the right AV is typically found within 5 mm of the inferior accessory hepatic vein. (15) When immediately transported to the laboratory, cortisol testing typically requires approximately 0.5–1 hour. While awaiting these results, the left AV can be sampled.

Not only is the right AV relatively difficult to select, but because of its early branching anatomy, once selected, the end-hole of the catheter is often opposed to a venous bifurcation, preventing aspiration of the catheter to collect the specimen. Furthermore, due to the diminutive nature of the vein, the wall can collapse around the catheter, also inhibiting aspiration. Strategies to allow for collection of the requisite 5–6 cc of venous blood include: using catheters with side holes near the tip, which may be created using 22-gauge needles; intermittent gentle suction using a syringe with air within it to reduce the negative pressure; allowing blood to drop slowly into a sample bottle rather than aspirating. (13-16)

The left AV is most often a branch of the left renal vein, and shares a common trunk with the inferior phrenic vein .The left AV is most often selected with a reverse curve catheter, such as a Simmons catheter, which may be advanced peripherally in the renal vein over a glide wire, then retracted until the tip carefully pops into the common trunk. Sampling may be performed from the common trunk, or from the AV using a microcatheter.

Failure to select the left AV, however, accounts for nearly a third of technical failures. Challenges in cannulating the left AV are primarily due to aberrant venous anatomy. Bilateral IVCs are present in less than 1% of patients, but left AV variants are present in 10% of people, most commonly circumaortic (6%), and less commonly retro aortic renal veins (4%) which are typically significantly more inferior from the IVC. Careful inspection of preprocedural cross-sectional imaging is essential to prepare for AVS in these cases.

Many centres utilize a sequential method with cosyntropin stimulation, as described earlier. Bilateral simultaneous sampling carries the theoretical benefit of minimizing the effect of hormone fluctuations over time, however is more technically challenging, as stable venous access to both AVs must be maintained. Given the more prolonged venous catheterization, intravenous heparin should be considered. Furthermore, if no cosyntropin is administered, careful attention to behavioural relaxation to minimize stress-related hormonal fluctuation is warranted (16)

Interpretation:

Selectivity Index (SI): Ratio of the adrenal venous cortisol concentration to the peripheral cortisol concentration on each side. SI ≥2.0 under unstimulated conditions or ≥3.0 during cosyntropin stimulation confirms that the blood sample was obtained from the adrenal vein.

Lateralization index (LI): Aldosterone/Cortisol ratio on the dominant side divided by the Aldosterone/Cortisol ratio on the contralateral side. A LI greater than (or equal to) 4 indicates lateralization of aldosterone secretion.

Because the normal adrenal gland produces cortisol in response to ACTH, venous cortisol levels are used as a positive control to determine that the AV is adequately sampled. The cortisol level in each adrenal vein (C_AV) is compared to peripheral samples taken from the IVC or right common femoral vein (C_peripheral), to generate a ratio (C_AV: Cperipheral), as cortisol should be several times greater than peripheral levels. A wide range of C_AV:C_peripheral index cut-offs have been used, from 1.1 to 5 with most centres using a cut off of 3 for AVS performed with cosyntropin stimulation, and 2 for AVS performed without stimulation. (15,16)

Complications :

1. Adrenal vein rupture and Haemorrhage. It usually resolves with conservative treatment and does not carry any sequelae. It can make subsequent adrenalectomy difficult due to adhesions.

2. Adrenal Vein Thrombosis and perforation.

3. Hypertensive crisis.

4. Adrenal insufficiency.

References:

1. Gordon RD. Mineralocorticoid hypertension. Lancet 1994;344:240 –243.

2. Gordon RD. Primary aldosteronism. J Endocrinol Invest 1995;18:495–511.

3. Stowasser M, Gordon RD, Rutherford JC, Nikwan NZ, Daunt N, Slater GJ. Diagnosis and management of primary aldosteronism. J Renin Angiotensin Aldosterone Syst 2001;2:156 –169. 4. Loh KC, Koay ES, Khaw MC, Emmanuel SC, Young WF Jr. Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore. J Clin Endocrinol Metab 2000;85:2854 – 2859.

5. Bernini G, Moretti A, Argenio G, Salvetti A. Primary aldosteronism in normokalaemic patients with adrenal incidentalomas. Eur J Endocrinol 2002;146:523–529.

6. Calhoun DA, Nishizaka MK, Zaman MA, Thakkar RB, Weissmann N. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002;40:892– 896.

7. Strauch B, Zelinka T, Hampf M, Berhardt R, Widimsky J Jr. Prevalence of primary hyperaldosteronism in the central Europe region. J Hum Hypertens 2003;17:349 –352.

8. Veglio F, Morello F, Rabbia F, Leotta G, Mulatero P. Recent advances in diagnosis and treatment of primary aldosteronism. Minerva Med 2003;94:259 –265.

9. Young WF, Klee GG. Primary aldosteronism: diagnostic evaluation. Endocrinol Metab Clin North Am 1988;17:367–395.

10. Gross MD, Falke THM, Shapiro B, Sandler MP. Adrenal glands. In: Endocrine imaging. Norwalk, Conn: Appleton & Lange, 1992; 271, 349.

11. Reznek RH, Armstrong P. The adrenal gland. Clin Endocrinol (Oxf) 1994;40:561–576.

12. Trigaux JP, Vandroogenbroek S, De Wispelaere JF, Lacrosse M, Jan J. Congenital anomalies of the inferior vena cava: evaluation with spiral CT. J Vasc Interv Radiol 1998;9:339 –345

13.Rossi GP, Barisa M, Allolio B, et al. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism. J Clin Endocrinol Metab. 2012;97(5):1606–1614.

14.Daunt N. Adrenal vein sampling: how to make it quick, easy, and successful. Radiographics. 2005;25 Suppl 1:S143–S158.

15. Espiner EA, Ross DG, Yandle TG, Richards AM, Hunt PJ. Predicting surgically remedial primary aldosteronism: role of adrenal scanning, posture testing, and adrenal vein sampling. J Clin Endocrinol Metab. 2003;88(8):3637–3644.

16. Rossi GP, Auchus RJ, Brown M, et al. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension. 2014;63(1):151–160.

17. Sung TY, Alobuia WM, Tyagi MV, Ghosh C, Kebebew E. Adrenal Vein Sampling to Distinguish Between Unilateral and Bilateral Primary Hyperaldosteronism: To ACTH Stimulate or Not?. J Clin Med. 2020;9(5):1447. Published 2020 May 13. doi:10.3390/jcm9051447